SHORT PAPER
Transformation of Arylaldoximes to Thioamides
379
The formation of akyl thioamides was limited by the un-
desired formation of the corresponding acid and amide,
which was produced from competing water hydrolysis re-
action of the alkyl nitrile; only 40–50% conversion into
thioamides was obtained.
References
(1) (a) Metzner, P. Synthesis 1992, 1185. (b) Haller, H. L. J.;
Barthel, W. F. US 2,358,925, 1994. (c) Leresque, C. L. US
2,560,296, 1951. (d) Le Hir de Fallois, L. P.; Lee, H. I.;
Timmons, P. R. US 7964621, 2011. (e) Jagodzinski, T. S.
Chem. Rev. 2003, 103, 197. (f) Lawesson, S. O.; Perregaard,
J.; Scheibye, S.; Meyer, H. J.; Thompson, I. Bull. Soc. Chim.
Belg. 1977, 86, 679. (g) Caddick, S. SyntheticPages
[Online], 2001, DOI: 10.1039/SP66;
In conclusion, a single-reagent-driven transformation of
aldoximes into thioamides via nitriles under solvent-free
conditions has been discovered. Thiophosphoryl chloride
has been utilized as the dehydrating agent as well as thion-
ating agent. The protocol was found to be of general ap-
plicability to arylaldoximes.
(2) (a) Oare, D. A.; Sanner, M. A.; Heathcock, C. H. J. Org.
Chem. 1990, 55, 132. (b) Heathcock, C. H.; Davidson, S. K.;
Mills, S. G.; Sanner, M. A. J. Org. Chem. 1992, 57, 2531.
(c) Magnus, P.; Mendoza, J. S.; Stamford, A.; Ladlow, M.;
Willis, P. J. Am. Chem. Soc. 1992, 114, 10232. (d) Kim, G.;
Chu-Moyer, M. Y.; Danishefsky, S. J.; Schulte, G. K. J. Am.
Chem. Soc. 1993, 115, 30. (e) Takahata, H.; Banba, Y.;
Mozumi, M.; Yamazaki, T. Heterocycles 1986, 24, 947.
(f) Takahata, H.; Yamazaki, T. Heterocycles 1988, 27,
1953. (g) Hurd, R. N.; Delmater, G. T. Chem. Rev 1961, 61,
45.
(3) (a) Mahammed, K. A.; Jayashankara, V. P.; Premsai Rai, N.;
Mohana Raju, K.; Arunachalam, P. N. Synlett 2009, 2338;
and references therein. (b) Kaboudin, B.; Elhamifar, D.
Synthesis 2006, 224. (c) Cho, D.; Ahn, J.; De Castro, K. A.;
Ahn, H.; Hakjune, R. Tetrahedron 2010, 66, 5583; and
references therein. (d) Bergman, J.; Pettersson, B.;
Hasimbegovic, V.; Svensson, P. H. J. Org. Chem. 2011, 76,
1546. (e) Kaboudin, B.; Malekzadeh, L. Synthesis 2011,
2807.
Reagents were obtained from commercial suppliers and used with-
out further purification. Aldoximes for entries 2, 4, and 8–12 were
prepared from the corresponding aldehydes by a reported proce-
dure.13 Solvents were purified by usual methods and stored over
molecular sieve. Freshly distilled PSCl3 was used. Melting points
were measured by Scientific MP-DS melting point apparatus. TLC
was performed using precoated aluminum sheets with silica gel
60F254. Column chromatographic purification of products was per-
formed on silica gel (60–120 mesh). 1H and 13C NMR spectra were
recorded on a Bruker Avance II 400 MHz. Mass spectra was ob-
tained in Agilent 5975C GC-MS. FT-IR spectra were recorded on a
Perkin Elmer IBX-200 spectrophotometer, using KBr pellets.
4-Bromobenzothioamide (3b); Typical Procedure
PSCl3 (102 mL, 1 mmol), H2O (18 mL, 1 mmol), and Et3N (139 mL,
1 mmol) was added to 4-bromobenzaldoxime (1b, 0.40 g, 2 mmol)
and mixed thoroughly. The mixture was heated at 70–75 °C for 15
min. At this stage conversion of oxime 1b to nitrile 2b was almost
complete. To this mixture were added PSCl3 (408 mL, 4 mmol), H2O
(72 mL, 4 mmol), and Et3N (973 mL, 7 mmol) and the mixture was
heated at 85–90 °C for 40 min, H2O (200 mL) was added and con-
tents were heated further at 80–85 °C for 3.5 h (alternatively, after
the addition of H2O the contents were thoroughly mixed and kept
overnight at r.t.). Neutralization with 10% NaHCO3 soln at 0–5 °C
resulted in precipitation of 4-bromothiobenzamide (3b) as light-yel-
low solid which was filtered under vacuum. The aqueous layer was
further extracted with EtOAc. The combined organic layers were
dried (anhyd Na2SO4), filtered, and concentrated under reduced
pressure. The residue was mixed with yellow solid and purified by
column chromatography (silica gel, EtOAc–hexane 1:9) to give
pure 3b as greenish yellow crystals; yield: 370 mg (86%); mp 189–
191 °C.
(4) Wan, J.-P.; Liu, Y. Synthesis 2010, 3943.
(5) (a) Sardarian, A. R.; Shahsavari-Fard, Z.; Shahsavari, H. R.;
Ebrahimi, Z. Tetrahedron Lett. 2007, 48, 2639; and
references therein. (b) Li, Z.; Lu, Z.; Zhu, A.; Feng, X.; Liu,
J.; Tian, G. Catal. Lett. 2008, 120, 105. (c) Kokare, N. D.;
Shinde, D. B. Monatsh. Chem. 2009, 140, 185. (d) Niknam,
K.; Karami, B.; Kiasat, A. R. Bull. Korean Chem. Soc. 2005,
26, 975. (e) Iranpoor, N.; Firouzabadi, H.; Arezu, J.; Mana,
T. Lett. Org. Chem. 2006, 3, 267. (f) Noei, J.; Khosropour,
A. R. Tetrahedron Lett. 2008, 49, 6969.
(6) (a) Yang, C.; Sun, D. Asian J. Chem. 2011, 23, 2112.
(b) Fee, D. C.; Gard, D. R.; Yang, C. Phosphorus
Compounds, In Kirk-Othmer Encyclopedia of Chemical
Technology; John Wiley & Sons: New York, 2005.
(c) Pathak, U.; Pandey, L. K.; Tank, R. J. Org. Chem. 2008,
73, 2890.
(7) Vimal, M.; Pathak, U.; Pandey, L. K.; Suryanarayana, M. V.
S. Synthesis 2011, 30.
(8) Kaboudin, B.; Elhamifar, D. Synthesis 2006, 224.
(9) Lin, P.-Y.; Ku, W.-S.; Shiao, M.-J. Synthesis 1992, 1219.
(10) Nagl, M.; Panuschka, C.; Barta, A.; Schmid, W. Synthesis
2008, 4012.
IR (KBr): 3287, 3135, 1629, 1583, 1069, 887 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.75 (br s, NH, 1 H), 7.73 (d,
J = 6.8 Hz, 2 H), 7.53 (d, J = 6.8 Hz, 2 H), 7.19 (br s, 1 H, NH).
13C NMR (100.6 MHz, CDCl3): d = 200.98, 181.12, 137.94, 131.16,
128.08, 126.67.
(11) Bagley, M. C.; Chapaneri, K.; Glover, C.; Merritt, E. A.
MS (EI, 70 eV): m/z = 215 [M+], 183, 181, 102, 75, 51.
Synlett 2004, 2615.
(12) Crane, L. J.; Anastassiadou, M.; Stigliani, J.-L.; Baziard-
Mouysset, G.; Payard, M. Tetrahedron 2004, 60, 5325.
(13) (a) Hajipour, A. R.; Mallakpour, S. E.; Imanzadeh, G.
J. Chem. Res., Synop. 1999, 228. (b) Hajipour, A. R.;
Rafiee, F.; Ruoho, A. E. J. Iran. Chem. Soc. 2011, 7, 114.
(c) Li, J.-T.; Chen, Y.-X.; Li, X.-L.; Deng, H.-J. Asian J.
Chem. 2007, 19, 2236. (d) Yates, J.; Willcox, T. J.; Wood,
D. A.; Haken, P. T. US 3,129,260, 1964.
Acknowledgement
The authors thank Dr. R. Vijayaraghavan, Director, DRDE for his
keen interest and encouragement.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 377–379